crossing96/oncoscreening huggingface dataset:
Influence of the Anesthetic Technique on Circulating Extracellular Vesicles in Bladder Cancer Patients Undergoing Radical Cystectomy: A Prospective, Randomized Trial.	Anesthetics have been shown to alter tumor progression and seem to influence surgical cancer outcome. Circulating extracellular vesicles as mediators of intercellular communication are involved in cancer progression and may be influenced by anesthetics. In this prospective, randomized study, effects of anesthetics on extracellular vesicles and associated micro-RNAs in bladder cancer patients undergoing radical cystectomy were tested. Extracellular vesicles from 51 patients at four perioperative time points receiving Propofol or Sevoflurane were extracted with polymer-based methods and quantified with a nanoparticle-tracking analysis. Vesicle-associated micro-RNAs were analyzed with a real-time polymerase chain reaction using array cards and single assays for tumor-associated miR-21-5p, miR-15a-5p, miR-17-5p and miR-451a. Plasma extracellular vesicle concentration (suture: fold change (fc) in Propofol at 4.1 ± 3.9 vs. Sevoflurane at 0.8 ± 0.5; p = 0.003) and associated miRNAs increased significantly (+30% post induction, +9% 30 Min surgery) in the Propofol group. Tumor-associated miRNAs increased during surgery in both groups (fc in miR-21-5p: 24.3 ± 10.2, p = 0.029; fc in miR-15a-5p: 9.7 ± 3.8, p = 0.027; fc in miR-17-5p: 5.4 ± 1.7, p = 0.014), whereas antitumor miR-451a increased in the Propofol group only (fc: 2.5 ± 0.6 vs. 1.0 ± 0.2; p = 0.022). Anesthetics influence extracellular vesicles and associated micro-RNAs of bladder cancer patients during surgery. Increased expression of antitumor micro-RNA may be an explanatory approach for decreased tumor cell viability after Propofol.	bladder
Construction and validation of a metabolism-associated gene signature for predicting the prognosis, immune landscape, and drug sensitivity in bladder cancer.	Tumor Metabolism is strongly correlated with prognosis. Nevertheless, the prognostic and therapeutic value of metabolic-associated genes in BCa patients has not been fully elucidated. First, in this study, metabolism-related differential expressed genes DEGs with prognostic value in BCa were determined. Through the consensus clustering algorithm, we identified two molecular clusters with significantly different clinicopathological features and survival prognosis. Next, a novel metabolism-related prognostic model was established. Its reliable predictive performance in BCa was verified by multiple external datasets. Multivariate Cox analysis exhibited that risk score were independent prognostic factors. Interestingly, GSEA enrichment analysis of GO, KEGG, and Hallmark gene sets showed that the biological processes and pathways associated with ECM and collagen binding in the high-risk group were significantly enriched. Notely, the model was also significantly correlated with drug sensitivity, immune cell infiltration, and immunotherapy efficacy prediction by the wilcox rank test and chi-square test. Based on the 7 immune infiltration algorithm, we found that Neutrophils, Myeloid dendritic cells, M2 macrophages, Cancer-associated fibroblasts, etc., were more concentrated in the high-risk group. Additionally, in the IMvigor210, GSE111636, GSE176307, or our Truce01 (registration number NCT04730219) cohorts, the expression levels of multiple model genes were significantly correlated with objective responses to anti-PD-1/anti-PD-L1 immunotherapy. Finally, the expression of interested model genes were verified in 10 pairs of BCa tissues and para-carcinoma tissues by the HPA and real-time fluorescent quantitative PCR. Altogether, the signature established and validated by us has high predictive power for the prognosis, immunotherapy responsiveness, and chemotherapy sensitivity of BCa.	bladder
The optimal intravesical maintenance chemotherapy scheme for the intermediate-risk group non-muscle-invasive bladder cancer.	OBJECTIVE: Although the current European Association of Urology(EAU) guideline recommends that patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) should accept intravesical chemotherapy or Calmette-Guerin (BCG) for no more than one year after transurethral resection of bladder tumor(TURBT), there is no consensus on the optimal duration of chemotherapy. Hence, we explored the optimal duration of maintenance intravesical chemotherapy in patients with intermediate-risk NMIBC. SUBJECTS AND METHODS: This was a real-world single-center retrospective cohort study. In total 158 patients with pathologically confirmed intermediate-risk NMIBC were included, who were divided into 4 subgroups based on the number of instillations given. We used Cox regression analysis and survival analysis chart to explore the 3-yr recurrence outcomes of tumor.The optimal duration was determined by receive operating characteristic curve (ROC). RESULTS: The median follow-up was 5.2 years. Compared with instillation for 1-2 months, the Hazard Ratios(HR) values of instillation for less than 1 month, maintenance instillation for 3-6 months and > 6 months were 3.57、1.57 and 0.22(95% CI 1.27-12.41;0.26-9.28;0.07-0.80, P = 0.03;0.62;0.02, respectively). We found a significant improvement in 3-yr relapse-free survival in intermediate-risk NMIBC patients who maintained intravesical instillation chemotherapy for longer than 6 months, and the best benefit was achieved with 10.5 months of maintenance chemotherapy by ROC. CONCLUSIONS: In our scheme, the optimal duration of intravesical instillation with pirrubicin is 10.5 months. This new understanding provides valuable experience for the precise medical treatment model of intermediate-risk NMIBC.	bladder
Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial.	BACKGROUND: Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved to treat locally advanced/metastatic urothelial carcinoma (mUC) in patients with susceptible FGFR3/2 alterations (FGFRalt) who progressed after platinum-containing chemotherapy. FGFR-altered tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti-programmed death-(ligand) 1 [PD-(L)1] treatment. This cohort in the randomized, open-label phase III THOR study assessed erdafitinib versus pembrolizumab in anti-PD-(L)1-naive patients with mUC. PATIENTS AND METHODS: Patients ≥18 years with unresectable advanced/mUC, with select FGFRalt, disease progression on one prior treatment, and who were anti-PD-(L)1-naive were randomized 1 : 1 to receive erdafitinib 8 mg once daily with pharmacodynamically guided uptitration to 9 mg or pembrolizumab 200 mg every 3 weeks. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: The intent-to-treat population (median follow-up 33 months) comprised 175 and 176 patients in the erdafitinib and pembrolizumab arms, respectively. There was no statistically significant difference in OS between erdafitinib and pembrolizumab [median 10.9 versus 11.1 months, respectively; hazard ratio (HR) 1.18; 95% confidence interval (CI) 0.92-1.51; P = 0.18]. Median PFS for erdafitinib and pembrolizumab was 4.4 and 2.7 months, respectively (HR 0.88; 95% CI 0.70-1.10). ORR was 40.0% and 21.6% (relative risk 1.85; 95% CI 1.32-2.59) and median duration of response was 4.3 and 14.4 months for erdafitinib and pembrolizumab, respectively. 64.7% and 50.9% of patients in the erdafitinib and pembrolizumab arms had ≥1 grade 3-4 adverse events (AEs); 5 (2.9%) and 12 (6.9%) patients, respectively, had AEs that led to death. CONCLUSIONS: Erdafitinib and pembrolizumab had similar median OS in this anti-PD-(L)1-naive, FGFR-altered mUC population. Outcomes with pembrolizumab were better than assumed and aligned with previous reports in non- FGFR-altered populations. Safety results were consistent with the known profiles for erdafitinib and pembrolizumab in this patient population.	bladder
Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma.	BACKGROUND: No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy. METHODS: In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes. RESULTS: A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively. CONCLUSIONS: Combination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.).	bladder
Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma.	BACKGROUND: Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) inhibitor approved for the treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3/2 alterations who have progression after platinum-containing chemotherapy. The effects of erdafitinib in patients with FGFR-altered metastatic urothelial carcinoma who have progression during or after treatment with checkpoint inhibitors (anti-programmed cell death protein 1 [PD-1] or anti-programmed death ligand 1 [PD-L1] agents) are unclear. METHODS: We conducted a global phase 3 trial of erdafitinib as compared with chemotherapy in patients with metastatic urothelial carcinoma with susceptible FGFR3/2 alterations who had progression after one or two previous treatments that included an anti-PD-1 or anti-PD-L1. Patients were randomly assigned in a 1:1 ratio to receive erdafitinib or the investigator's choice of chemotherapy (docetaxel or vinflunine). The primary end point was overall survival. RESULTS: A total of 266 patients underwent randomization: 136 to the erdafitinib group and 130 to the chemotherapy group. The median follow-up was 15.9 months. The median overall survival was significantly longer with erdafitinib than with chemotherapy (12.1 months vs. 7.8 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.47 to 0.88; P = 0.005). The median progression-free survival was also longer with erdafitinib than with chemotherapy (5.6 months vs. 2.7 months; hazard ratio for progression or death, 0.58; 95% CI, 0.44 to 0.78; P<0.001). The incidence of grade 3 or 4 treatment-related adverse events was similar in the two groups (45.9% in the erdafitinib group and 46.4% in the chemotherapy group). Treatment-related adverse events that led to death were less common with erdafitinib than with chemotherapy (in 0.7% vs. 5.4% of patients). CONCLUSIONS: Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti-PD-1 or anti-PD-L1 treatment. (Funded by Janssen Research and Development; THOR ClinicalTrials.gov number, NCT03390504.).	bladder
Intra-arterial chemotherapy plus BCG, a promising combination adjuvant treatment for high-risk NMIBC.	PURPOSE: To develop a novel combination therapy for high-risk nonmuscle-invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT), namely, intra-arterial chemotherapy (IAC) plus BCG immunotherapy, and to compare the feasibility and safety of the 2 therapies. MATERIALS AND METHODS: A retrospective study was conducted on the data of 119 patients who were diagnosed with high-risk NMIBC and underwent TURBT in the past 5 years. Those who did not complete the treatment were excluded, and the remaining 98 patients were divided into 2 groups: both groups received intravesical BCG immunotherapy, while the BCG+IAC group received 4 courses of extra intra-arterial chemotherapy. Clinical and follow-up data were processed using statistical software. RESULTS: The recurrence rate was 22.2% in the BCG+IAC group and 35.8% in the BCG group, whereas the progression rates were 8.9% and 24.5%, respectively. In the Kaplan-Meier plot, a statistically significant difference was observed with respect to recurrence-free survival (p = 0.025), as well as the progression-free survival of the two groups was similar (p = 0.019). A total of 22.2% of the patients with adverse effects of IAC and 79.6% of patients suffered from adverse reactions to BCG immunotherapy, and most of the adverse effects were mild and tolerable. Univariate and multivariate analysis indicated that multifocal and treatment were independent risk factors for recurrence, while the history of recurrence and treatment were independent risk factors for progression. CONCLUSION: IAC could be a promising auxiliary treatment for BCG immunotherapy in decreasing the recurrence and progression rate of high-risk NMIBC with little additional toxicity.	bladder
Does neo-adjuvant chemotherapy improve the negative effect of lymphovascular invasion in survival after radical cystectomy?	PURPOSE: There is a lack of studies in the literature to evaluate the impact of the specific benefit of the use of neo-adjuvant chemotherapy (NAC) on the negative effect of lymphovascular invasion (LVI) on prognosis. We aimed to evaluate the survival differences of patients according to the presence of LVI with and without administration of NAC before radical cystectomy (RC). MATERIALS AND METHODS: We retrospectively evaluated data of the patients who underwent RC with pelvic lymphadenectomy and urinary diversion for bladder cancer recorded in the bladder cancer database of the Turkish Uro-oncology Association between 2007 and 2021. Patient demographics, follow-up time and overall survival (OS) were noted. RESULTS: A total of 633 subjects included in the analyses. Median follow-up time was 24 months (IQR 12-54). Five years OS of the whole cohort was 55.1%. This was 54.7% and 59.9% in NAC- and NAC+ groups (P = 0.683), respectively. It was also 35.7% and 65.7% in LVI+ and LVI- patients (P < 0.0001), respectively. There was a significant difference between LVI+ and LVI- patients (33.2% vs. 68.2%, P < 0.0001) in NAC- group, but similar 5-year OS was found (53.2% vs. 64.5%, P = 0.552) in NAC+ group. In multivariable analyses, female gender, pN stages, presence of variant histology and LVI were significant independent predictive factors for OS in the whole cohort and in the NAC- group. However, gender association, pN stages and LVI lost significance in NAC+ group. CONCLUSION: Presence of LVI significantly reduced OS, and the NAC treatment improved the negative effects of LVI on OS. Our findings encourage the use of NAC before RC.	bladder
Comparison of perioperative outcomes and complications between intracorporeal, extracorporeal, and hybrid ileal conduit urinary diversion during robot-assisted radical cystectomy: a comparative propensity score-matched analysis from nationwide multi-institutional study in Japan.	BACKGROUND: To investigate the impact of different urinary diversion (UD) techniques on the peri- and postoperative complications of robot-assisted radical cystectomy (RARC) with ileal conduit. METHODS: We retrospectively analyzed 373 patients undergoing RARC with ileal conduit at 11 institutions in Japan between April 2018 and December 2021. Propensity score weighting was performed to adjust for confounding factors such as age, sex, body mass index, performance status, American Society of Anesthesiologists score, previous abdominal surgery, neoadjuvant chemotherapy, and preoperative high T stage (≥ cT3) and high N stage (≥ cN1). Perioperative complications were then compared among three groups: extracorporeal, intracorporeal, and hybrid urinary diversion (ECUD, ICUD, and HUD, respectively). RESULTS: A total of 150, 68, and 155 patients received ECUD, HUD, and ICUD, respectively. Bowel reconstruction time and UD time were significantly shorter in the ECUD group (p < 0.001), and console time was significantly longer and blood loss was significantly higher in the ICUD group (p < 0.001). For postoperative complications (Clavien-Dindo Classification grade ≥ 3), surgical site infection (p = 0.004), pelvic abscess (p = 0.013), anastomotic urine leak (p = 0.007), and pelvic organ prolapse (p = 0.011) significantly occurred in the ECUD group. For all grades, ileus was more common in the HUD group, whereas anastomotic stricture was more common in the ECUD group compared with the other groups (p < 0.05). CONCLUSIONS: Severe complications did not increase after HUD and ICUD compared with ECUD; however, console time tended to be longer and blood loss was slightly higher during RARC.	bladder
Real-world outcomes of adjuvant immunotherapy candidates with upper tract urothelial carcinoma: results of a multicenter cohort study.	BACKGROUND: Recent clinical trials have reported improved disease-free survival rates of patients with stage pT3-4/ypT2-4 or pN + upper tract urothelial carcinoma (UTUC) on adjuvant nivolumab therapy. However, the appropriateness of the patient selection criteria used in clinical practice remains uncertain. METHODS: We retrospectively analyzed 895 patients who underwent nephroureterectomy to treat UTUC. The patients were divided into two groups: grade pT3-4 and/or pN + without neoadjuvant chemotherapy (NAC) or grade ypT2-4 and/or ypN + on NAC (adjuvant immunotherapy candidates) and others (not candidates for adjuvant immunotherapy). Kaplan-Meier curves were drawn to assess the oncological outcomes, including recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Cox proportional hazards models were used to identify significant prognostic factors for oncological outcomes. RESULTS: The Kaplan-Meier curves revealed notably inferior RFS, CSS, and OS of patients who were candidates for adjuvant immunotherapy. Multivariate analysis revealed that pathological T and N grade and lymphovascular invasion (LVI) status were independent risk factors for poor RFS, CSS, and OS. CONCLUSION: In total, 44.8% of patients were candidates for adjuvant immunotherapy. In addition to pathological T and N status, LVI was a significant predictor of survival, and may thus play a pivotal role in the selection of patients eligible for adjuvant immunotherapy.	bladder
Identification of pyroptosis-related lncRNA subtype and signature predicts the prognosis in bladder cancer.	Pyroptosis is a new type of programmed cell death involved in all stages of tumorigenesis. Herein, a comprehensive study was conducted to evaluate the prognostic significance of pyroptosis-related lncRNAs in bladder cancer. Consensus clustering analysis was performed to identify the subclusters of bladder cancer. The prognostic pyroptosis-related lncRNA signature was constructed using LASSO Cox regression analysis. Consensus clustering identified 2 clusters of bladder cancer. Interestingly, significant differences in the ESTIMAE score, immune cell infiltration and immune checkpoint expression were obtained between the 2 clusters. A signature consisting of 11 pyroptosis-related lncRNAs was established and it had a good performance in predicting the overall survival rate of bladder cancer, with an AUC of 0.713. Moreover, pyroptosis-related lncRNA signature acted as a risk factor in bladder cancer. Bladder cancer patients with high-risk score had a higher tumor grade and higher clinical stage. A significant correlation was obtained between the risk score and immune cell infiltration. The expression of most checkpoints was higher in bladder cancer patients with high-risk score. A novel pyroptosis-related lncRNA signature was identified with prognostic value for bladder cancer patients. Pyroptosis-related lncRNAs have a potential role in cancer immunology and may serve as prognostic or therapeutic targets in bladder cancer.	bladder
Navigating the Rapidly Evolving Advanced Urothelial Carcinoma Treatment Landscape: Insights from Italian Experts.	PURPOSE OF REVIEW: To discuss recent advances in the treatment of advanced urothelial carcinoma (UC) and how best to incorporate new therapies into clinical practice. RECENT FINDINGS: There have been several recent practice-changing phase 2 and 3 trials of immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and targeted agents in advanced UC. Based on data from these trials, ICIs can be used as first-line maintenance therapy in patients who do not progress on platinum-based chemotherapy, second-line therapy for those with progression, and first-line therapy in cisplatin-ineligible patients with PD-L1 expression; ADCs and targeted agents provide later-line treatment options. Despite substantial progress in the treatment of advanced UC, there are still many uncertainties, including the optimal treatment sequence for novel agents, and reliable predictive biomarkers to aid in treatment selection. There is also an unmet need for effective treatment options in patients unfit for any platinum-based chemotherapy.	bladder